The overall goal of the proposed R&D program is to develop improved methodologies and manufacturing processes for the isolation of the marine natural product bryostatin 1 which is derived from the marine byrozoan Bugula neritina. Bryostatin 1 is currently in Phase II clinical trials in the US against melanomas, lymphomas and renal cells. While harvesting the bryozoan with consistent sources of the active agent will become a significant portion of the supply problem, large-scale manufacturing of the natural product agent will also pose significant challenges to processing logistics and manufacturing costs. In our Phase I research effort, we showed that supercritical fluid extraction and chromatography techniques can be utilized to very rapidly isolate bryostatin I from Bugula with several hundred fold (370) improvements m purity in times less than 30 minutes, with very high recovery efficiencies (approximately-100%), and in an environmentally friendly manner. In our Phase II R&D effort, we plan to further improve the supercritical fluid process and modify an existing pilot-plant for the isolation of ultra-pure bryostatin 1. We plan to collaborate with CalBioMarine who will supply both naturally occurring and aquacultured quantities of the "sea moss" B. neritina. PROPOSED COMMERCIAL APPLICATION: The developed process will facilitate the manufacturing of bryostatin 1 and therapeutic analogy and increase their availability for preclinical and clinical use by the National Cancer Institute, and pharmaceutical companies such as Bristol-Myers Squibb.